Chapter 3 – Neurodegenerative Disorders Introduction Neurodegenerative disorders: disorders that involve progressive loss of function or destruction of neurons or various structures of the brain Acquired disorders: disorders caused by an accident, insult, or disease process coming from a source outside the cortex a. Many find that individual requires care outside family environment People don’t usually die from dementia but from something else that takes advantage of a nonintact central nervous system. • May be unable to fight off viruses • Most frequent cause of death is pneumonia Affects 5-8% of people older than 65 and 25-50% of people older than 85.
Transcript
Chapter 3 – Neurodegenerative Disorders
Introduction
Neurodegenerative disorders: disorders that involve progressive loss of function or destruction of neurons or various structures of the brain
Acquired disorders: disorders caused by an accident, insult, or disease process coming from a source outside the cortex
Degenerative Disorders
Degenerative disorders: difficulties with destruction of neurons and/or specific areas within the central nervous system
• In many cases, the loss of neurons/tissue is not reparable and the loss of ability is permanent
Cortical Dementias
Def.: damage within the cerebral cortex, which leads to symptoms of dementia.
Dementia is usually described with behaviours falling into 3 stages
1. Behaviours that may deviate from the norm for the individual. The individual may not be aware of this
a. Example: small changes in personality and memory lapses
2. Individual often notices memory problems and tries to conceal them from others. Confabulation (individual makes up a story to account for memory loss) may occur.
a. As stage 2 progresses, the individual may become geographically lost
b. May engage in activities that are dangerous to self or others
c. Sundowning: worsening of symptoms as the day progresses
d. Families begin to consider placement in treatment facilities
3. Serious cognitive deterioration along with problems with self-care
a. Many find that individual requires care outside family environment
People don’t usually die from dementia but from something else that takes advantage of a nonintact central nervous system.
• May be unable to fight off viruses
• Most frequent cause of death is pneumonia
Affects 5-8% of people older than 65 and 25-50% of people older than 85.
Alzheimer’s Type Dementia
Def.: dementia characterized by neurofibrillary tangles and amyloid plaques; diagnosis cannot be made until autopsy but is termed Alzheimer’s type based on behavioural symptoms
• Neurofibrillary tangles: composed of tau protein; tangles of dead tissue in the brain. Develop when microtubules become twisted. Volume of tangles obstructs living tissue and often strangle it.
o Tau: protein that maintains microtubules structure but is altered, allowing tubules to twist. Believed to develop from abnormal phosphorylation
• Amyloid plaques: deposits of aluminum silicate and amyloid peptides (beta-amyloid) believed to cause loss of neurons and vascular damage. Obstruct normal tissue.
• These plaques/tangles normally appear in aging people but Alzheimer’s is diagnosed by the extent of these and the regions of the brain that they gravitate towards.
Loss of neurons is a common feature, especially in the temporal area.
• If neurons can’t communicate with major memory areas within cortex, significant memory loss may occur.
Loss of neurons also leads to changes in anatomical structure, may point to enlargement of ventricles in Alzheimer’s disease.
Present in 10% of people aged 65+ and 25% over 80. Also has inherited genetic component.
• If a person has a first-degree relative with the disease, it doubles their chance of acquiring the disease.
Three well-established risk factors for Alzheimer’s:
• Age
• The gene for the protein apolipoprotein E (Apo E) on chromosome 19. Is a naturally occurring protein, helps to carry phospholipids and cholesterol within the body.
o The E4 allele (any one of a number of viable DNA codings that occupy a given position on a chromosome) has been linked to various disorders including Alzheimer’s.
• Down syndrome. Almost all individuals with this show mental and physical deterioration characteristic of Alzheimer’s if they live longer than 30-40 years.
Other factors:
• Being female
• Lower levels of education
• Exposure to aluminum in drinking water
• Traumatic brain injury – controversial. The more serious an injury, the more likely the person will develop the disease.
• Low level of estrogen in postmenopausal women – controversial. May be confounded with educational level and socioeconomic status
Most distinguishing cognitive feature of Alzheimer’s is severe verbal memory difficulties.
• Difficulty is in all stages of memory
• Other issues:
o Orientation
o Psychomotor performance
o Language/speech fluency
o Complex reasoning
Treatment for Alzheimer’s:
• Drinking red wine as preventative (antioxidants have protective effect)
• Medications that stop the development of amyloid plaques
• Cognitive deficits treatment is usually with anticholinesterase inhibitors that enhance cholinergic function
o People either respond to this or they don’t
• Antidepressants
• May use typical or atypical antipsychotic medications
Frontotemporal Dementias
Degenerative disorders of the frontal and temporal lobes. The rest of the cortex remains mostly unharmed.
• Slow onset and progression
• Usually between 40-65 years of age
Symptoms are very similar to Alzheimer’s and, in later stages, almost indistinguishable. Differentiation:
• Changes in social behaviour and personality
• Lack of insight
• Stereotypic behaviours – repeating of a behavioural sequence
• Eating a great deal of food
• Speech and language changes
• Extrapyrimidal symptoms
• Primitive reflexes
Etiology is unknown but 40-50% if cases are transmitted by autosomal dominate inheritance = dominant non-sex-linked gene
• Greater than average incidence of brain trauma 4 years prior to occurrence of symptoms
Before, was called Pick’s disease – that is now thought to be a subtype of FTD. Set apart from other FTDs by Pick bodies: composed of tau protein and shaped differently than neurofibrillary tangles
Dementia with Lewy Bodies
About 20% of patients with dementia.
Symptoms include progressive dementia, extrapyramidal signs similar to Parkinson’s, visual hallucinations, delusions, and possibly severe cognitive fluctuations.
More rapid decline than other dementias.
Presence of Lewy bodies: protein deposits throughout the cortex, paralimbic area, and in the substantia nigra.
Improvement has been shown with using cholinesterase inhibitors
Subcortical Dementias
Affect subcortical brain structures. The behavioural changes that differentiate from cortical dementias:
1. Cognitive slowing with problems in attention and concentration, executive disturbances including impaired concept manipulation, visuospatial abnormalities, and memory difficulties that affect retrieval
2. Absence of aphasia (loss of expressive or receptive language), apraxia (inability to perform purposeful movements), and agnosia (inability to recognize sensory input)
3. Emotional features including apathy, depression, and personality changes.
Have movement difficulties – extrapyramidal motor system: modulates movement and maintains muscle tone and posture.
Parkinson’s Disease/Parkinsonism
Def.: Movement disorder with attendant symptoms.
Involuntary tremulous motion with lessened muscle power. May include difficulties moving from resting to walking (vice versa), tendency to bend forward while walking, and cognitive/emotional sequelae.
• Not all patients exhibit these
• Almost always present is ‘resting tremor’ which disappears during movement and in sleep
• Another classic symptom is ‘masked faces’, a lack of facial expressions
• Depression is one of most common symptoms but severity appears unrelated to severity of motor symptoms
The disease is associated with the depletion of the neurotransmitter dopamine in the basal ganglia, subthalamic nucleus, substantia nigra, and the connections between them all.
Etiology is unknown. Typically affects individuals in their fifties.
• There may be genetic inheritance
• May be related to viral encephalitis, drugs with dopamine antagonistic properties, toxic substances, and vascular disease.
PD does have an incidence of dementia that ranges from 2-93%.
Treatment:
• Medical focuses on the alleviation of symptoms or slowing disease progression
o L-Dopa is used to replace dopamine depletion in the subtantia nigra
• Surgical treatments include lesions or placing a deep brain stimulator in the regions of the globus pallidus, subthalamic nuclei, or ventral intermediate thalamic nuclei
Huntington’s Disease
Anatomically caused by atrophy of the GABAergic neurons fo the caudate nucleus and putamen in the corpus striatrum.
• Gamma-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter.
• Atrophy may also affect the cerebellum, thalamic nucleu, and other subcortical tissue. Reported effects on the basal ganglia as well.
Steadily progressive disease, tends to affect individual between 10-20 years of age.
• First symptoms are mild and often ignored
• As motor symptoms are involved, the disease becomes visible to the individual and others
• Pneumonia is most common cause of death
Hereditary condition – passes from generation to generation
• Caused by an excess number of trinucleotide CAG repeats (cystosine, adenine, and guanine) on chromosome 4
• Is an autosomal dominant disease – half of all offspring of a carrier parent will acquire the disease if they live long enough
• Affects more Caucasians
Treatment is usually palliatative. Neuroleptic medications are often used to deal with spasmodic movements
Progressive Supranuclear Palsy
Also known as Steele-Richardson-Olszewski disorder.
Classic feature is an inability to look downward.
• Similar motor/cognitive/emotional disturbances as with other dementias
• Progression of cognitive decline appears to be greater and is consistent with degeneration of both cortical and subcortical regions
• Sites of lesions are in the upper brain stem to the basal ganglia and may include the limbic structures and basal ganglia
• Degeneration appears to disconnect ascending pathways from these structures to the prefrontal cortex
Nonfamilial condition, tends to develop in 60s. May have connection to environmental toxins.
Has limited response to dopaminergic or anticholonergic drugs.
Progressive Disorders of the Central Nervous System
Multiple Sclerosis
Def.: Disease caused by destruction of the myelin sheath that covers the axons. At the demyelinated sites, multiple discrete plaques are formed by astrocytes.
Classic symptoms:
• Weakness
• Stiffness
• Lack of coordination
• Gait disturbances
• Bladder and bowel difficulties
• Sexual dysfunction
• Sensory changes
• Heat sensitivity
• Fatigue
Cognitive impairment is evident in 40-60% of patients. Memory is one of most commonly affected areas. The extent of cognitive deficits is related to location and extent of damage.
Tends to follow one of several courses:
• Relapsing-remitting: most common. Characterized by clearly defined diseases relapses. Recovery can be full or with residual deficit. No progression of disease between relapses
• Secondary-progressive: second most common. First characterized by relapsing-remitting course then progression. Relapses and remissions may or may not occur
• Primary-progressive: third most common. Unremitting disease progression from onset for most patients but occasional stabilization and improvement in others. No clear relapse.
• Progressive-relapsing: least common. Disease progression from onset. Acute relapses also occur from which patients may or may not recover.
MS does not generally shorten life span.
Genetic factors influence susceptibility. More common in women. Normal age of onset is 30.
High-dose corticosteroids are used in acute attacks. Neuropsychological effects have been shown with the use of medications that there is an increase in cognitive functioning and memory. Cholinesterase inhibitors have also shown to help with this.
Normal Pressure Hydrocephalus
Def.: Results from the accumulation of cerebrospinal fluid caused by lack of reabsorption or obstruction of its flow.
• Sometime obstruction can be identified
This condition can be corrected. But if not treated, can produce progressive deterioration.
This is a disease of old age, not similar to the hydrocephalus that is sometimes present after birth
The buildup of CSF greatly enlarges the ventricles that then causes pressure within the brain.
Untreated, it becomes a dementia with symptoms like gait disorder, urinary incontinence, and cognitive impairment.
Can be treated with a shunt that directs CSF to the heart where it is then redirected to the circulatory system.
Cerebrovascular Disorders
All involve difficulty with circulatory system, vessels that are important for the transport of oxygen and glucose to the brain.
Cerebrovascular Accident
Cerebrovascular accident (CVA) or stroke is most common.
• Stroke: caused by a disruption of the flow of oxygen and glucose to the brain.
o Process of disruption can be sudden or progressively worse over the years
CVA results in cerebral ischemia: restricted blood flow to the cerebral area of the brain.
• If it lasts long enough, can cause an infarct: localized necrosis resulting from obstruction of a blood vessel
Strokes are usually caused by one of two processes:
1. Thrombic strokes are caused by a thrombus: fibrinous clot formed in a blood vessel. As it grows, it narrows the opening of the blood vessel and reduces blood flow.
a. Most common cause is atherosclerosis – fatty deposits build up within the vessel and narrow it
2. Embolic strokes are caused by a clump or plug of thrombic material that has broken away from the blood vessel wall and travels to other areas, usually the brain (Embolus)
Sometimes caused by a hemorrhage: massive bleeding into a structure of the brain
• Common causes: hypertension or introduction of a foreign object (ex. Bullet)
Risk factors for stroke: age; cardiac disease; transient ischemic attacks; hypertension; and diabetes mellitus.
Symptoms tend to be focused on one side of the body. Stroke hits one hemisphere and paralyze (paresis) or partially paralyze other side of body (hemiparesis).
• Left side: verbal and comprehension difficulties, aphasia as common symptom. Tend toward depression and view symptoms as more serious than they are.
• Right side: perceptual and visual-spatial deficits. Tend to exhibit indifference and downplay symptoms.
Transient Ischemic Attacks
Def.: Temporary obstructions of a blood vessel for less than 24 hours – usually last only minutes.
• Many people are not aware of these as they do not generally produce significant or long-lasting effects.
Characterized as stroke-like phenomena. Tend to occur on one side of the body with behavioural effects on one side of the body.
Tend to pave the way for strokes. Even mild TIAs will leave some cognitive impairment.
Treatment is continual use of antiplatelet therapy (aspirin). Removal of atherosclerotic plaques may be necessary if there is significant arterial narrowing.
Vascular Dementia
Cortical atherosclerotic dementia: multiple infarcts of the large blood vessels which supply blood to the brain leads to symptoms of dementia
Subcortical atherosclerotic dementia: multiple infarcts of the smaller blood vessels lead to difficulties in blood supply to subcortical areas; leads to symptoms of dementia
Lacunar strokes: small infarcts in the basal ganglia, internal capsule, and pons. Leads to sensory and motor symptoms
Binswanger’s disease: caused by multiple infarcts in the periventricular area and cerebral white matter with demyelization; causes symptoms of dementia
• Cognitive and executive functions are symptoms
No medication approved for vascular dementia. Treatment is preventive and supportive,
Hypertension
Def.: elevated blood pressure. Read as systolic over diastolic
• Systolic pressure: maximum arterial pressure during contraction of the left ventricle of the heart
• Diastolic pressure: pressure in arteries when the heart is at rest
Normal blood pressure is 120/80. Generally, 140/90 is considered high blood pressure.
Hypertension is a major predictive factor in any form of cardiovascular disorder. Often goes undiagnosed. Risk factors:
• Obesity, excessive use of salt, excessive use of alcohol, lack of exercise, and smoking
Alone, can cause cognitive deficits. Longer it goes undetected, the greater the deficits.
Antihypertension medication may slow reaction time or cause memory deficits.
Migraine Headaches
Second most common category of neurological disorders.
Often thought to be signaled by the presence of an aura: sensation that precedes the onset of certain disorders, such as epileptic seizure or migraine headache.
• Migraine without aura = common migraine
• Migraine with aura = classic migraine
Symptoms vary between patients. Aura usually begins half hour before the headache.
Women experience them more than men. Some evidence of hereditary component. Tend to occur in people who experience major stress, too much/too little sleep, and consume certain foods.
Vascular theory of migraine: aura is associated with intracranial vasoconstriction and the headache with an inflammatory reaction around the walls of dilated cephalic vessels = pulsating aspects of the headache.
Neurogenic theory of migraine: headache is caused by the serotonergic and adrenergic pain-modulating systems. Indicates a drop in serotonin levels with migraines and a decrease in migraine pain with the administration of antidepressants that works with this neurotransmitter.
Brain Tumours
Tumour: mass of new and abnormal tissue that is not physically beneficial to its surrounding structure.
Secondary brain tumours are more common than primary brain tumours in adults, while the opposite is true in children.
• Primary brain tumours: develop within the brain
• Secondary brain tumours: develop outside the brain
Graded on level of severity – 1: least serious. 4: most serious.
Primary Brain Tumours
Gliomas
Def.: tumours that develop from glial cells within the brain
Most common types of primary brain tumours in adults.
• Malignant astrocytic tumours, glioblastoma multiform, and anaplastic astrocytomas are most common glial tumours in adults
Glioblastoma multiform: grow quickly and highly malignant. Tend to appear later in life.
Malignant astrocytomas (tumours caused by growth of astrocytes; tend to not grow very quickly and are rarely malignant) tend to infiltrate brain tissue and are difficult to remove surgically. Radiation and chemotherapy are the usual treatments but are usually palliative.
Average survival time for glioblastomas with treatment is one year. Anaplastic astrocytomas is 2-4 years,
Oligodendrogliomas: glioma which is thought to originate from oligodendrocytes of the brain
• Usually of lower grade
Meningiomas: develops from the cells that cover the meninges. Very often do not involve brain tissue and can be easily removed.
• Second most common form of brain tumour in adults
Central Nervous System Lymphoma
Def.: caused by lesions that tend to cluster around the ventricles. Patients may exhibit cognitive and/or behavioural changes usually associated with subcortical involvement.
Treatment is cranial irradiation and corticosteroids. Survival time from diagnosis is 12-18 months
Secondary Brain Tumours
Metastatic Brain Tumours
Metastatic intracranial neoplasms: cancerous tumour originating in different parts of the body and then transported to the central nervous system.
Most common sources are the lungs, breasts, skin, gastrointestinal tract, heart, and kidney.
They tend to grow faster and show effects sooner than one developed within the brain.
Increases intracranial pressure. Seizures. Paralysis and aphasia. May cause certain hormones or endocrine functions to change.
Survival time is usually 4-6 months.
Metabolic and Endocrine Disorders
Secondary effect of a systematic difficulty located elsewhere in the body.
Many of the symptoms include cognitive disturbances (confusion or delirium). Psychological symptoms are more common with endocrine disorders than metabolic.
Diabetes Mellitus
Def.: Type I diabetes. Severe, chronic form of diabetes caused by insufficient production of insulin and resulting in abnormal metabolism of carbohydrates, fats, and proteins. Type II diabetes. Mild form of diabetes that typically appears first in childhood and is exacerbated by obesity and inactive lifestyle.
Children with diabetes mellitus have a higher risk than the general population for cognitive impairment.
Diabetics are at higher risk for dementia. Often have other difficulties like hypertension and cerebrovascular disease.
Hypothyroidism
Cognitive difficulties are common, along with symptoms of fatigue, lethargy, and sluggishness. May exhibit memory and concentration difficulties. Serious difficulties such as delirium and hallucinations can occur when hypothyroidism is severe.
Liver Disease
Liver controls removal of toxic substances from the body. Symptoms vary by toxicity and usually include attentional difficulties and response slowing,
Uremia
Caused by kidney failure. Symptoms include apathy, lethargy, and cognitive dysfunction. Even when treated with dialysis, patients display memory and learning problems and reduced mental flexibility.
Seizures
Epilepsy
Def.: any of various neurological disorders characterized by sudden and recurring attacks of motor, sensory, or psychic malfunction with or without loss of consciousness or convulsive seizures.
Caused by hyperexcitability and hyposynchronous discharge of the nerve cells of the brain. The brain is technically short circuited.
Focal seizures or partial seizures have localized origin. Generalized seizures involve large regions of both hemispheres simultaneously.
Symptomatic: cause of seizure is known. Idiopathic: cause of seizure is not known.
Partial seizures: come from specific focal area of brain, may be without loss of consciousness (simple) and may include only one modality of expression.
• Can progress
Complex partial seizures: includes loss of consciousness.
Primary generalized seizures may be nonconvulsive in which consciousness is briefly lost or convulsive which involves major motor manifestations (grand mal seizures).
Tends to present at greater levels in families as either general lessening of the seizure threshold or an inherited predisposition to seizures.
Memory and learning problems are common among many epileptics. Personality disorders are more common. There is a higher rate of comorbidity for psychological disorders.
After seizure, many patients may exhibit shame or anger along with confusion.
Treatment for most people involves antiepileptic medications.
Surgery has been performed to relieve the spread of seizures from one side of the body.
• Most common is an anterior temporal lobectomy
• Vagal nerve stimulation – tends to improve seizure control but does not completely eradicate the seizures
